Effectiveness and Safety of Tofacitinib in Patients With Extensive and Recalcitrant Alopecia Areata
Study Details
Study Description
Brief Summary
The objective of this study is to assess the safety and efficacy of Tofacitinib in treating patients with extensive and recalcitrant Alopecia Areata (AA), along with to evaluate the economic impact of the patients that may be from changing in their quality of life. There are patients with severe AA who may have little or no improvement from the treatment by diphenylcyclopropenone (DPCP) or topical steroid with minoxidil but instead having positive response from the treatment with Janus kinase(JAK) inhibitor such as Tofacitinib or Ruxolitinib. For the best of my knowledge, there was no previous study in using Tofacitinib to treat severe AA before in Thailand.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Alopecia areata (AA) or spot baldness, is a condition in which hair falls off from areas of the body. It often happens on the scalp, causing a few bald spots and it may result in psychological stress even though people are generally healthy. AA is believed to be an autoimmune disease progressing from a breach in the immune privilege of the hair follicles that causes hair to fall out in small patches, it may remain unnoticeable until the patches eventually connect and then become noticeable. It can develop slowly, and also recur after years between occurrences.
By standard AA treatment guideline, DPCP is the first treatment protocol and may follow with anthralin or minoxidil. This oldy but goody treatment gives a good result of 75% in spotty hair loss and 25% in total baldness. The new invention of treatment has been introduced in the past 2 years by using JAK inhibitor, an oral medicine such as Tofacitinib and Ruxolitinib. This treatment gives a good outcome so far in this short period of time, 54-81.9% of patients had over 50% increase of hair grows over the original protocol. The theory is that JAK inhibitors would inhibit interferon-gamma and interleukin-15 signal between white blood cell and hair follicle which reducing the rate of destroying hair follicles.
The investigators propose the study to assess the safety and efficacy of Tofacitinib for extensive and recalcitrant AA and to evaluate the economic impact effecting the AA patients. Tofacitinib is an expensive medicine and needed to be taken up to 6 months to finish the course to have a best outcome so it is not a popular choice of AA treatment at present time unless it can show a promising result in recalcitrant AA.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tofacitinib All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata. |
Drug: Tofacitinib
Tofacitinib is an oral medicine in Janus kinase inhibitor 3 group which has been approved by FDA in treating Rheumatoid Arthritis. It has ability to inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the cause of hair loss.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Responders vs Non-Responders Using SALT Score [48 weeks]
The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss.
Secondary Outcome Measures
- Side Effects From Tofacitinib [48 weeks]
Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Thai volunteers age between 18 and 60 years old.
-
Volunteers must be patients who suffer from severe AA more than 50% of the entire scalp.
-
Volunteers must be patients who are able to complete the monthly treatment at least in the first 6 months.
Exclusion Criteria:
-
Patients who suffer from other hair diseases such as: Telogen effluvium, Trichotillomania, Tinea capitis
-
Patients who have other diseases that can have an impact on hair loss or temporary hair loss condition with in 6 months prior to the study such as: thyroid problems, liver disease, malnutrition, hearth disease, neurological disease, gastrointestinal disorders, sexually transmitted disease, cancer, psychiatric disease.
-
Patients with AA who received treatment with either steroid, Anthralin or DPCP application within 1 month before the selection or patients who had oral or injection from steroid or other medication for hair loss treatment within 3 months before the selection.
-
Woman with pregnancy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Dermatology | Bangkok | Thailand |
Sponsors and Collaborators
- Institute of Dermatology, Thailand
Investigators
- Principal Investigator: Chinmanat Lekhavat, MD, Institute of Dermatology
Study Documents (Full-Text)
More Information
Publications
- Alkhalifah A, Alsantali A, Wang E, McElwee KJ, Shapiro J. Alopecia areata update: part II. Treatment. J Am Acad Dermatol. 2010 Feb;62(2):191-202, quiz 203-4. doi: 10.1016/j.jaad.2009.10.031. Review.
- Craiglow BG, Liu LY, King BA. Tofacitinib for the treatment of alopecia areata and variants in adolescents. J Am Acad Dermatol. 2017 Jan;76(1):29-32. doi: 10.1016/j.jaad.2016.09.006. Epub 2016 Nov 2.
- Divito SJ, Kupper TS. Inhibiting Janus kinases to treat alopecia areata. Nat Med. 2014 Sep;20(9):989-90. doi: 10.1038/nm.3685.
- Ibrahim O, Bayart CB, Hogan S, Piliang M, Bergfeld WF. Treatment of Alopecia Areata With Tofacitinib. JAMA Dermatol. 2017 Jun 1;153(6):600-602. doi: 10.1001/jamadermatol.2017.0001.
- Liu LY, Craiglow BG, Dai F, King BA. Tofacitinib for the treatment of severe alopecia areata and variants: A study of 90 patients. J Am Acad Dermatol. 2017 Jan;76(1):22-28. doi: 10.1016/j.jaad.2016.09.007. Epub 2016 Nov 2.
- Taylor CR, Hawk JL. PUVA treatment of alopecia areata partialis, totalis and universalis: audit of 10 years' experience at St John's Institute of Dermatology. Br J Dermatol. 1995 Dec;133(6):914-8.
- Tosti A, Iorizzo M, Botta GL, Milani M. Efficacy and safety of a new clobetasol propionate 0.05% foam in alopecia areata: a randomized, double-blind placebo-controlled trial. J Eur Acad Dermatol Venereol. 2006 Nov;20(10):1243-7.
- IRB/IEB 004/2562
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Nineteen participants who met the inclusion criteria were enrolled and received 10 mg/day oral tofacitinib. |
| Arm/Group Title | Tofacitinib |
|---|---|
| Arm/Group Description | All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata. Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss. |
| Period Title: Overall Study | |
| STARTED | 19 |
| COMPLETED | 19 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Tofacitinib |
|---|---|
| Arm/Group Description | All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata. Tofacitinib is the Janus kinase inhibitor, which FDA has approved for Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss. |
| Overall Participants | 19 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
32.68
(8.75)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
12
63.2%
|
| Male |
7
36.8%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| Asian |
19
100%
|
| Region of Enrollment (Count of Participants) | |
| Thailand |
19
100%
|
| Baseline SALT score (score) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [score] |
95.11
(14.24)
|
Outcome Measures
| Title | Number of Responders vs Non-Responders Using SALT Score |
|---|---|
| Description | The Severity of Alopecia Tool (SALT) is a measurement procedure used by dermatologists to determine the percentage of scalp hair loss. The SALT system divides the scalp into 4 areas: Top has 4 sections of 10% total are 40%, back has 4 sections of 6% total are 24% and the 2 sides, left and right, each has 2 sections of 4% and 2 sections of 5% total of 18% and 36% combined. In the beginning, the area of hair loss would be measured by checking each area for hair loss and determining the bald spots combined per SALT scale then keeping the record as SALT baseline (SALT). The total SALT score is measured 0-100%, with higher values representing greater hair loss. |
| Time Frame | 48 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tofacitinib |
|---|---|
| Arm/Group Description | All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata. Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss. |
| Measure Participants | 19 |
| Responders (SALT score improved >=50%) |
9
47.4%
|
| Non-responders (SALT score improved < 50%) |
10
52.6%
|
| Title | Side Effects From Tofacitinib |
|---|---|
| Description | Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48. |
| Time Frame | 48 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Tofacitinib |
|---|---|
| Arm/Group Description | All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata. Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss. |
| Measure Participants | 19 |
| Dyslipidemia |
9
47.4%
|
| Upper respiratory tract infection |
6
31.6%
|
| Tuberculosis |
1
5.3%
|
| Myalgia |
1
5.3%
|
| Acne |
2
10.5%
|
| Weight gain |
1
5.3%
|
| Constipation |
1
5.3%
|
Adverse Events
| Time Frame | Patients came back for follow-up every month during a total of 24 weeks of treatments and at weeks 28,36 and 48. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Tofacitinib | |
| Arm/Group Description | All participants will take Tofacitinib 5 mg twice daily for 24 weeks to treat extensive and recalcitrant alopecia areata. Tofacitinib: Tofacitinib is an oral medicine in the Janus kinase inhibitor 3 groups which FDA has approved in treating Rheumatoid Arthritis. It can inhibit nerve signal Interferon-ɣ and Interleukin-15 between white blood cell(WBC) and the nucleus of hair follicle cell causing the production of WBC type CD8+NKG2D+ T cell to slow down which this type of WBC is one of the causes of hair loss. | |
All Cause Mortality |
||
| Tofacitinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/19 (0%) | |
Serious Adverse Events |
||
| Tofacitinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/19 (5.3%) | |
| Gastrointestinal disorders | ||
| Intestinal tuberculosis | 1/19 (5.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Tofacitinib | ||
| Affected / at Risk (%) | # Events | |
| Total | 9/19 (47.4%) | |
| Gastrointestinal disorders | ||
| Constipation | 1/19 (5.3%) | 1 |
| Infections and infestations | ||
| Upper respiratory tract infection | 6/19 (31.6%) | 6 |
| Metabolism and nutrition disorders | ||
| Dyslipidemia | 9/19 (47.4%) | 9 |
| Weight gain | 1/19 (5.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Myalgia | 1/19 (5.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Acne | 2/19 (10.5%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Chinmanat Lekhavat (My old last name is Tangjaturonrusamee.) |
|---|---|
| Organization | Institute of Dermatology |
| Phone | +660847607474 |
| chinmanat@hotmail.com |
- IRB/IEB 004/2562